The aminoshikimic acid pathway in bacteria as source of precursors for the synthesis of antibacterial and antiviral compounds

• Published in: Journal of industrial microbiology & biotechnology Vol. 48; no. 9-10; p. 1
• Main Authors: Escalante, Adelfo, Mendoza-Flores, Rubén, Gosset, Guillermo, Bolívar, Francisco
• Format: Journal Article
• Language: English
• Published: Germany Oxford University Press 23-12-2021
• Subjects: Actinomycetales; Amino acids; Anti-Bacterial Agents; Antiviral Agents - pharmacology; Bacteria; Care and treatment; Epidemics; Influenza; Metabolic Engineering and Synthetic Biology; Phosphates; Physiological aspects; Rifabutin; Rifapentine; Rifaximin; Shikimic Acid - analogs & derivatives; Antimicrobial, Antiviral compounds; AHBA; Metabolic engineering; Aminoshikimic acid pathway; Aromatic metabolism
• ISSN: 1367-5435; 1476-5535
• DOI: 10.1093/jimb/kuab053

The aminoshikimic acid (ASA) pathway comprises a series of reactions resulting in the synthesis of 3-amino-5-hydroxybenzoic acid (AHBA), present in bacteria such as Amycolatopsis mediterranei and Streptomyces. AHBA is the precursor for synthesizing the mC7N units, the characteristic structural component of ansamycins and mitomycins antibiotics, compounds with important antimicrobial and anticancer activities. Furthermore, aminoshikimic acid, another relevant intermediate of the ASA pathway, is an attractive candidate for a precursor for oseltamivir phosphate synthesis, the most potent anti-influenza neuraminidase inhibitor treatment of both seasonal and pandemic influenza. This review discusses the relevance of the key intermediate AHBA as a scaffold molecule to synthesize diverse ansamycins and mitomycins. We describe the structure and control of the expression of the model biosynthetic cluster rif in A. mediterranei to synthesize ansamycins and review several current pharmaceutical applications of these molecules. Additionally, we discuss some relevant strategies developed for overproducing these chemicals, focusing on the relevance of the ASA pathway intermediates kanosamine, AHAB, and ASA.